Back to resultsStudy of MLN4924, a Novel Inhibitor of Nedd8 Activating Enzyme, in Adult Patients With Lymphoma or Multiple Myeloma
Primary Purpose
Hematologic Malignancies, Multiple Myeloma, Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MLN4924
Sponsored by
About this trial
This is an interventional treatment trial for Hematologic Malignancies
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Patients must have a confirmed diagnosis of lymphoma (Waldenstrom's macroglobulinemia is permitted) or multiple myeloma that is relapsed and/or refractory after at least 2 prior standard chemotherapeutic regimens and for which no curative option exists.
1. As of Protocol Amendment 7, patients in the expansion cohort, Schedule E, must specifically have Hodgkin lymphoma, DLBCL-GCB subtype, DLBCL-non-GCB subtype, or Mantle Cell Lymphoma (MCL). Patients with multiple myeloma will no longer be evaluated as a part of this study.
Tumor that is evaluable by radiography, serum or urine electrophoresis (for patients with multiple myeloma), or clinical evaluations.
1. As of Protocol Amendment 7, tumor that is evaluable by radiography or clinical evaluations.
- Suitable venous access for the conduct of blood sampling for MLN4924
- Adequate Organ Function
Exclusion Criteria:
- Systemic antineoplastic therapy within 21 days preceding first dose of study treatment, or rituximab therapy within 2 months preceding first dose of study treatment (unless there was evidence of PD since their last dose of rituximab).
- Treatment with corticosteroids within 7 days preceding first dose of study treatment.
- Prior treatment with radiation therapy involving >25% of bone marrow; Any radiotherapy within 14 days before first dose of study treatment.
- Treatment with CYP3A inducers within 14 days before the first dose of MLN4924. Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the study.
- Patients requiring Coumadin who cannot be switched to a low molecular weight heparin should not be considered for this study.
- Absolute neutrophil count less than 1,000/mm3; platelet count less than 75,000/mm3.
- Calculated creatinine clearance less than or equal to 50 mL/minute.
Sites / Locations
- Winship Cancer Institute
- Roswell Park Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
MLN4924
Outcomes
Primary Outcome Measures
Evaluation of safety and tolerability
Secondary Outcome Measures
Disease response
Full Information
NCT ID
NCT00722488
First Posted
July 23, 2008
Last Updated
November 15, 2013
Sponsor
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00722488
Brief Title
Study of MLN4924, a Novel Inhibitor of Nedd8 Activating Enzyme, in Adult Patients With Lymphoma or Multiple Myeloma
Official Title
An Open-Label, Dose Escalation, Phase I Study of MLN4924, a Novel Inhibitor of Nedd8 Activating Enzyme, in Adult Patients With Lymphoma or Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2013
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
4. Oversight
5. Study Description
Brief Summary
This is an open-label, multicenter, phase 1, dose escalation study of MLN4924 in adult patients with lymphoma or multiple myeloma. The patient population will consist of adults with a confirmed diagnosis of lymphoma (Waldenstrom's macroglobulinemia is permitted) or multiple myeloma that is relapsed and/or refractory after at least 2 prior standard chemotherapeutic regimens and for which no curative option exists.
Patients in the expansion cohort, Schedule E, must specifically have Hodgkin lymphoma, DLBCL-GCB subtype, DLBCL-non-GCB subtype, or Mantle Cell Lymphoma (MCL). Patients with multiple myeloma will no longer be evaluated as a part of this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancies, Multiple Myeloma, Lymphoma, Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
MLN4924
Intervention Type
Drug
Intervention Name(s)
MLN4924
Intervention Description
Intravenous dose 100 mg/m2 on a Days 1,4,8,11 schedule within a 21-day treatment cycle. Treatment may continue until disease progression or unacceptable toxicity develops.
Primary Outcome Measure Information:
Title
Evaluation of safety and tolerability
Time Frame
12 months (maximum duration of therapy)
Secondary Outcome Measure Information:
Title
Disease response
Time Frame
12 months (maximum duration of therapy)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Patients must have a confirmed diagnosis of lymphoma (Waldenstrom's macroglobulinemia is permitted) or multiple myeloma that is relapsed and/or refractory after at least 2 prior standard chemotherapeutic regimens and for which no curative option exists.
1. As of Protocol Amendment 7, patients in the expansion cohort, Schedule E, must specifically have Hodgkin lymphoma, DLBCL-GCB subtype, DLBCL-non-GCB subtype, or Mantle Cell Lymphoma (MCL). Patients with multiple myeloma will no longer be evaluated as a part of this study.
Tumor that is evaluable by radiography, serum or urine electrophoresis (for patients with multiple myeloma), or clinical evaluations.
1. As of Protocol Amendment 7, tumor that is evaluable by radiography or clinical evaluations.
Suitable venous access for the conduct of blood sampling for MLN4924
Adequate Organ Function
Exclusion Criteria:
Systemic antineoplastic therapy within 21 days preceding first dose of study treatment, or rituximab therapy within 2 months preceding first dose of study treatment (unless there was evidence of PD since their last dose of rituximab).
Treatment with corticosteroids within 7 days preceding first dose of study treatment.
Prior treatment with radiation therapy involving >25% of bone marrow; Any radiotherapy within 14 days before first dose of study treatment.
Treatment with CYP3A inducers within 14 days before the first dose of MLN4924. Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the study.
Patients requiring Coumadin who cannot be switched to a low molecular weight heparin should not be considered for this study.
Absolute neutrophil count less than 1,000/mm3; platelet count less than 75,000/mm3.
Calculated creatinine clearance less than or equal to 50 mL/minute.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31355467
Citation
Faessel HM, Mould DR, Zhou X, Faller DV, Sedarati F, Venkatakrishnan K. Population pharmacokinetics of pevonedistat alone or in combination with standard of care in patients with solid tumours or haematological malignancies. Br J Clin Pharmacol. 2019 Nov;85(11):2568-2579. doi: 10.1111/bcp.14078. Epub 2019 Sep 4.
Results Reference
derived
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Study of MLN4924, a Novel Inhibitor of Nedd8 Activating Enzyme, in Adult Patients With Lymphoma or Multiple Myeloma
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